Genetic Test for Cleft Lip and Palate

A new genetic test can help predict whether parents who have one child with the "isolated” form of cleft lip or palate are likely to have a second child with the same birth defect. Isolated clefts, which are clefts in children with no other birth defects, account for 70% of all cases.

The test, which requires only a blood sample, is based on distinct mutations in and around the gene IRF6, which encodes a specific protein that plays a vital role in the normal formation of the lips, palate, skin, and genitalia during the early stages of development. Researchers noticed a variation in the DNA sequence that might cause isolated clefts by interfering somehow with the normal biologic activities of the IRF6 protein during tissue and organ development.

To test their hypothesis, the researchers focused on a pool of 1,986 families in Europe, South America, and Asia, with a history of isolated clefts. "We wanted to see whether the variation could be found across multiple ethnic and ancestral groups, or if it was confined to a single population,” explained senior author Jeffrey Murray, M.D., a scientist at the University of Iowa (Iowa City, IA, USA).

When the researchers looked at the gene and nearby regions, they identified a total of 36 DNA variations, nine of which seemed to be associated with clefting. The individual variations were then assembled into a haplotype. This haplotype was found to be over-transmitted in some families with isolated clefts, suggesting a predictive association with the defect, found to be true in The Philippines, Denmark, and the United States. The risk of parents with this haplotype having a second child with isolated cleft lip and palate is about 12%. These findings were reported in the August 19, 2004, issue of The New England Journal of Medicine.




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